The invention relates to apparatus and methods for photocoagulating tissue, reinforced by administering a chromophore; in general, the chromophore is indocyanine green (ICG) which has an absorption peak in blood at 800 nanometers (nm) and lying in the range 760 nm to 840 nm as a function of dosage. This is the wavelength at which presently-available diode lasers emit.
Such methods have already been proposed for destroying neo vessels (new blood vessels) under the retina (article by David R. Guyer et al. xe2x80x9cIndocyanine green angiography and dye-enhanced diode laser photocoagulationxe2x80x9d, Seminars in Ophthalmology, Vol. 7, No. 3, 1992) and in dermatology for photocoagulating cutaneous angiodysplasias situated at depth and difficult to access for treatment by lasers emitting in the absorption spectrum of hemoglobin.
The use of ICG for photocoagulation nevertheless encounters numerous difficulties, of which the main difficulty is its short lifetime in plasma, to which there can be added its progressive diffusion away from the new vessels into which it has been injected. The use of continuous injection for compensating short lifetime reduces selectivity because of the diffusion.
The invention seeks to reduce the consequences of short lifetime by using the observation that the dynamics of ICG elimination can be modelled with an approximation that is satisfactory for a period of about 10 minutes after administration in the form of a decreasing mono-exponential function having a time constant that lies in practice in the range 3 minutes (min) to 5 min.
Consequently, the invention proposes a laser photocoagulator comprising:
a laser emitting at a wavelength lying in the absorption spectrum of ICG and provided with focusing means; and
a laser power supply module programmed or controlled so that the mean flux density F at the focus starting from an initial instant varies as an increasing function of time that never departs by more than 10% from an increasing mono-exponential having the form F=F0(1xe2x88x92exe2x88x92t/xcfx84) where F is the initial flux density and xcfx84 is a time constant lying in the range 3 min to 5 min.
Time t is measured from the administration of ICG and not from the beginning of laser treatment. F0 is selected to have a value that is as high as possible within the limit set by ensuring selectivity of action on the vessels that have received the ICG. The present initial F0 is selected as a function of the injected dose of ICG and of the time interval that elapses between injection and the first laser shot on the vessels. In practice, the injected dose of ICG will not exceed about 15 milligrams per kilogram (mg/kg) of tissue. The corresponding initial flux density is a decreasing and substantially linear function of dose starting from an initial value, for a zero dose, of the order of 300 joules per square centimeter (J/cm2) for a zero dose.
Varying fluence (flux density) over time makes it possible to cause reproducible thermal damage to occur from one operation to another and to conserve selective photocoagulation of those vessels which have received ICG, providing that not more than about 10 minutes is allowed to elapse from injection.
The administered power, and thus the fluence, is adjusted by acting on an available parameter of the laser used. In the common case of a pulse laser, the modulus is programmed or controlled to cause the flux density to vary by modifying unit power and/or duration. The frequency of successive shots in a sequence can also be adjustable.
For example, it can be stated that a diode laser emitting at 810 nm and delivering a power of 0.8 watts (W) with pulses being applied over a period of up to 10 seconds (s) during which flux density can be varied from 60 J/cm2 to 360 J/cm2 gives good results when destroying vessels in the dermis.
Ordinary laser photocoagulators generally have an external connector enabling duration, spacing, and power of pulses to be controlled from an external control module. Such a module can include, in particular, a processor having a memory containing a program that determines how the power delivered by the laser photocoagulator should vary over time. The invention also provides such a control module programmed so as to cause flux density to vary in application of the above-defined function, and a program which, when loaded into a control module, causes said function to be executed.
In a variant embodiment of the invention, the photocoagulator device is associated with means that continuously supply an estimate of the concentration of ICG in the blood, and it is programmed in such a manner as to adjust mean flux density continuously as a function of the estimate so as to achieve compensation. The concentration estimating means can be used for continuously adjusting flux density by correcting the law stored in the power supply module. These means can also replace the stored relationship. Finally, they can be used for adjusting the time constant xcfx84.
By way of example, these means can be constituted by apparatus for measuring ICG concentration and sold under the name xe2x80x9cICG Clearance Meterxe2x80x9d by Daiichi Pharmaceutical Co., where the estimate of concentration is based on the absorption of infrared light by the terminal phalaux of a finger. Such apparatus is used at present only for determining the rate at which ICG is eliminated by the liver and thus for evaluating possible deterioration of liver function.
It is also important to observe that the problem to be solved is associated with the rapid rate of decrease in the concentration in the blood of a chromophore, in particular ICG, that is injected to enable photocoagulation by thermal action, and is not associated with the fact tumor cells eliminate a photosensitizing agent more quickly than healthy cells during laser treatment of a cancer.